Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease.

Methods

We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014).

Findings

12 children met the case definition (median age 11·5 years [IQR 6·75–15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5·75–8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits.

Interpretation

We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities.

Genetic sequencing of a virus found in respiratory secretions of children in California and Colorado who suffered from paralysis or muscle weakness last fall reveals that they were infected with a mutated strain of enterovirus D68 that is closer to polio than other strains common in previous years.

The study, published Monday in Lancet Infectious Diseases, sheds new light on one of the most troubling medical mysteries of recent years. Amid a nationwide outbreak of severe respiratory illness, doctors at hospitals nationwide began to report that they were seeing an alarming number of children with unexplained weakness in an arm or a leg to complete paralysis that required them to be put on ventilators.

Treating physicians noted that many of the children appeared to be infected with enterovirus D68, but researchers were cautious about drawing a causal link because virus had been bouncing around the world since the 1960s and had typically only caused breathing issues such as coughing and wheezing.

While the research does not provide a definitive link -- that would only be established if the virus were found in the spinal fluid and it was not -- it provides the strongest evidence to date of the link between enterovirus D68 and paralysis. The researchers theorize that the reason the virus was not found in the spinal fluid could be because the samples were taken too late. Scientists also tested the children for the presence of other pathogens capable of causing the symptoms but didn't find other viruses, bacteria, fungi or parasites.

The new research reveals that the children had a novel strain of the virus, called B1, which emerged about four years ago. That strain has only five to six coding differences from previous strains that were commonly found in the United States but each of those are mutated in the direction of polio or another nerve-damaging virus known as EV-D70.

"These are changes that may have made the virus more polio-like," said Charles Chiu, an associate professor at the University of California-San Francisco who worked on the study.

While the study identified D68 as a possible trigger of the paralysis, it was not able to shed any light on another key question: Why have some children been affected so severely while others have been fine?

The study included a pair of siblings with a 100 percent genetically identical strain of the virus. One experienced muscle weakness and paralysis while the other only experienced upper respiratory symptoms.

January 29, 2015

Since August 2014, more than 100 children and young adults in the United States have developed a mysterious paralysis. Many of them had fevers before losing strength in one or more limbs, and the cases coincided with a wider epidemic of a little-known respiratory pathogen. That virus, enterovirus D68 (EV-D68), is the leading candidate for the cause of the paralysis, which few children have recovered from.

Yet researchers have not definitively linked the two, or determined how the virus could cause the children’s symptoms. A study published on 28 January in The Lancet that describes a cluster of cases from Denver, Colorado, strengthens the link, but falls short of providing a 'smoking gun'. Here is what we know about the virus — and what scientists are trying to find out.

What is EV-D68?

It belongs to the enterovirus family, which includes poliovirus and the pathogens that cause common colds; it is most similar to the rhinoviruses that cause respiratory infections. Although EV-D68 was first isolated in the 1960s, it is relatively uncommon among enteroviruses circulating worldwide.

However, since August 2014, the virus has been linked to more than 1,000 respiratory infections in the United States, some of them severe, and France has seen cases, too. John Watson, a medical epidemiologist at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, says that last year, EV-D68 was the predominant type of enterovirus circulating in the country. “That’s a first,” he says. Genome sequencing of viruses recovered from respiratory cases in St Louis, Missouri, shows that the EV-D68 strain circulating in the United States is most closely related to viruses that caused a pneumonia-like illness in three children in Thailand in 2011.

What is the evidence that links EV-D68 to the cases of paralysis?

It has mostly to do with the timing: the cases of paralysis appeared during a wider outbreak of EV-D68, says Watson, whose team at the CDC’s Division of Viral Diseases is investigating the link. Researchers detected EV-D68 in nasal swabs from 8 out 41 people with paralysis who were tested, and another 9 people tested positive for related viruses.

January 14, 2015

Since last summer, public-health officials have been trying to figure out why more than 100 children in dozens of states have suffered from a polio-like weakness in their limbs.

And while authorities have not found a direct link to the severe respiratory illness that affected children across the country last year, they are exploring whether that nationwide outbreak may be tied to this mysterious situation.

There have been 103 confirmed reports of children who have developed the illness, which is called “acute flaccid myelitis,” according to the Centers for Disease Control and Prevention. These cases, which span 34 states, have almost all led to the hospitalization of the affected children, with some of them put on breathing machines.

Last fall, the CDC began testing cases that occurred after Aug. 1. They had tested 88 cases by mid-November and found some possible trends, but the ultimate cause of the illnesses were still unclear. A handful of cases involved children who had been affected by the enterovirus D68 outbreak, but the CDC cautioned that no causal relationship between the illness could be confirmed by that time. There are also other viruses that can cause illnesses with symptoms like the ones currently being seen, the CDC noted.

The possible tie to the enterovirus D68 (or EV-D68) outbreak is particularly worrisome, given how widespread this virus became. More than 1,100 people — again, most of them children — have been affected since last August.

This number is likely severely underestimating how many were infected, as the CDC says there were presumably “millions” of mild infections in people who did not get tested. The virus was ultimately confirmed in 49 states and the District of Columbia.

In September, as the enterovirus outbreak continued, health officials in Colorado explored a cluster of nine children suffering from weakness and paralysis. Some of these children tested positive for the enterovirus.

Still, another concern in this latest illness is how many children have not seen any improvement since developing symptoms. Two out of three have said they had some improvement, compared to one in three who showed none. So far, only one child with the illness had fully recovered, the CDC says.

December 07, 2014

In addition to providing the usual scourges of malaria, dengue, seasonal influenza, antibiotic resistant bacteria and pneumonia, 2014 has provided us with a number of new, or sometimes simply transplanted, disease threats around the world.

A reminder that in our highly mobile and interconnected world, a disease threat anywhere can easily become a disease threat everywhere.

What follows is a superb retrospective on the outbreaks of the past year: H5N1, H7N9, chikungunya, MERS, Ebola, and EV-D68.

The ECDC communicable disease threats report is a weekly bulletin intended for epidemiologists and health professionals in the area of communicable disease prevention and control.

Summarising information gathered by ECDC through its epidemic intelligence activities regarding communicable disease threats of concern to the European Union, it also provides updates on the global situation and changes in the epidemiology of communicable diseases with potential to affect Europe, including diseases that are the focus of eradication efforts.

October 05, 2014

The B.C. Centre for Disease Control confirmed Saturday that another child in the province has been diagnosed with enterovirus-D68, an infectious disease that can cause breathing problems for children.

That puts the number of confirmed cases of EV-D68 in B.C. at nine.

Dr. Danuta Skowronski, an infectious diseases specialist at the BC Centre for Disease Control, says the child, betwen the ages of five and nine, is from the Lower Mainland and has been hospitalized with respiratory illness.

She said the cases in B.C. are sporadic and spread among the health authorities except for Vancouver Island. She added that none is linked to an outbreak of the disease.

On Tuesday, the centre said two boys were hospitalized after developing polio-like symptoms. One child between five and 10 years old is experiencing weakness in one arm that has not improved for nearly a month, while a teen aged 15 to 20 also developed weakness in one arm and was put on a breathing machine.

Health officials said the children had no connection to each other and lived several hundred kilometres apart.

Enterovirus D68 tends to affect younger children and can lead to coughing, wheezing, dehydration and loss of appetite. While EV-D68 is considered a common cold, it puts young children at risk, which is why officials having been advising schools, hospitals, parents and caregivers to be on a heightened alert.

Children with asthma or other underlying respiratory conditions are the most commonly affected.

October 03, 2014

In his 16 years as a pediatric neurologist, Brandon Meaney has never seen a situation like the one unfolding now at McMaster Children’s Hospital in Hamilton, Ont.

In the space of two weeks, four children have turned up with polio-like symptoms that doctors cannot explain. All have been vaccinated against polio and none had contact with each other before arriving at the hospital.

Although Dr. Meaney, the head of pediatric neurology at McMaster, said his hospital sees an average of four to six patients every year with sudden muscle weakness and partial paralysis, the cause of their illness is usually swiftly diagnosed as something like Guillain-Barré syndrome, an immune disorder.

“But the polio-like presentation?” he said. “I haven’t seen a case in over 10 years.”

So far this month, nine other cases of patients with similar polio-like symptoms have been reported elsewhere in Canada: two in British Columbia, four in the Calgary area and three at the Hospital for Sick Children in Toronto.

It’s too early to determine the ultimate prognosis for these patients, though some have begun to recover the movement they had lost.

Dr. Meaney and his counterparts across Canada and the United States are trying to figure out if these cases of out-of-the-blue partial paralysis are caused by enterovirus D-68 [EV-D68], a previously rare strain of cold virus that has spread more widely in North America this year, causing severe respiratory illness in some children.

Clusters of children with unexplained neurological symptoms and sudden paralysis have also emerged in Colorado recently, and in California between June of 2012 and June of this year.

“There is a mystery here,” Dr. Meaney said. “With all the darn cases and all the attention and the [U.S. Centers for Disease Control and Prevention] and everyone focused on it, we’ve got to at some point be able to pin it down.”

Linking the muscle weakness and partial paralysis cases to EV-D68 is no straightfoward task. In B.C., the two afflicted patients have tested positive for EV-D68, but in Hamilton only one has. Two other Hamilton patients have tested negative for EV-D68, while tests on the fourth patient are pending. Results are also still pending for the three patients in Toronto and the four in Calgary.